This "Public Health Response Research" project is submitted as one of six research projects in the application for a multi-institutional Middle Atlantic Regional Center of Excellence (RCE) for Biodefense and Emerging Infectious Diseases Research. The objective of this project is to immediately accelerate the clinical evaluation and deployment of new biomedical technologies that may be crucial for an effective public health 0response to a bioterrorism or emerging infectious disease event. The project encompasses three sub-projects, all of which involve immediate evaluation of novel biotechnologies in human subjects. Sub-project 1 is designed to rapidly transition novel needle-free technologies for vaccine administration into routine use. The specific aims of this sub-project are to evaluate cutaneously administered immunostimulatory patches to boost responses to anthrax vaccines and botulinum toxoid, to evaluate intranasal administration of recombinant anthrax protective antigen, and to evaluate jet injector administration of recombinant anthrax protective antigen. Sub-project 2 is designed to use measurements of peripheral blood lymphocyte gene expression profiles from vaccinated persons to improve the diagnosis, prognosis, and prevention of smallpox vaccine adverse events. The specific aims of this sub-project are to define the natural history of vaccinia-induced immune dysregulation, to correlate favorable and unfavorable outcomes with specific gene transcript profiles, and to use the technology to identify individuals at increased risk of vaccine adverse reactions. Sub-project 3 is designed to evaluate rapid innovative genomics- and proteomics-based diagnostic technologies in real emergency room settings. The specific aims of this project are to evaluate novel universal bacterial and viral diagnostics, to evaluate blood lymphocyte gene expression profiles in common febrile illnesses, like influenza, that could be mistaken for bioterror threats, and to use mass spectrometry-based proteomics on respired air from patients to diagnose acute pulmonary infections. As additional new genomics- and proteomics-based technologies are generated from the Middle Atlantic RCE and elsewhere, they will be rapidly evaluated for their utility in the public heath biodefense response.